title: P(II) signal transduction proteins are ATPases whose activity is regulated by 2-oxoglutarate.
abstract: P(II) proteins are one of the most widespread families of signal transduction proteins in nature, being ubiquitous throughout bacteria, archaea, and plants. In all these organisms, P(II) proteins coordinate many facets of nitrogen metabolism by interacting with and regulating the activities of enzymes, transcription factors, and membrane transport proteins. The primary mode of signal perception by P(II) proteins derives from their ability to bind the effector molecules 2-oxoglutarate (2-OG) and ATP or ADP. The role of 2-OG as an indicator of cellular nitrogen status is well understood, but the function of ATP/ADP binding has remained unresolved. We have now shown that the Escherichia coli P(II) protein, GlnK, has an ATPase activity that is inhibited by 2-OG. Hence, when a drop in the cellular 2-OG pool signals nitrogen sufficiency, 2-OG depletion of GlnK causes bound ATP to be hydrolyzed to ADP, leading to a conformational change in the protein. We propose that the role of ATP/ADP binding in E. coli GlnK is to effect a 2-OG-dependent molecular switch that drives a conformational change in the T loops of the P(II) protein. We have further shown that two other P(II) proteins, Azospirillum brasilense GlnZ and Arabidopsis thaliana P(II), have a similar ATPase activity, and we therefore suggest that this switch mechanism is likely to be a general property of most members of the P(II) protein family.
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom.
authors.forename: Martha V
authors.initials: MV
authors.lastname: Radchenko
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thornton
authors.forename: Mike
authors.initials: M
authors.lastname: Merrick
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D007656:Ketoglutaric Acids / Q000378:metabolism*; D009154:Mutation; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D051922:PII Nitrogen Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: C111096:AmtB protein, E coli; D029681:Arabidopsis Proteins; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; C100965:GlnZ protein, Azospirillum brasilense; D007656:Ketoglutaric Acids; D051922:PII Nitrogen Regulatory Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C497878:glnK protein, E coli; D009713:Nucleotidyltransferases; D000251:Adenosine Triphosphatases
keywords: ATP hydrolysis; metabolic signalling; nitrogen regulation